CXC and CC chemokines induced in human renal epithelial cells by inflammatory cytokines

Human renal epithelial cells might play an important role during the allograft rejection by producing chemokines in response to proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β produced by endothelial and epithelial cells early after transplantation. The production of chemokines allows inflammatory cells to be drawn into the kidney graft and therefore plays a critical role in the pathophysiologic processes that lead to the rejection of renal transplant. In this process, two chemokine superfamilies, the CC and the CXC chemokines, are the most important. The CC chemokines target mainly monocytes and T lymphocytes, while most of the CXC chemokines attract neutrophils. We showed in our study that in vitro, in unstimulated cells, basal mRNA expression of CXC chemokines (Groα, Groβ, Groy, ENA-78 and GCP-2, IL-8) that attract neutrophils was detectable and expression of these genes and chemokine release were increased in TNF-α- and IL-1β-induced renal epithelial cells. Most of the CC chemokines [monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein 1 beta (MIP-1β), regulated upon activation, normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein (MIP-3α)] showed detectable mRNA expression only after stimulation with proinflammatory cytokines and not in control cells. TNF-α seems to induce preferably the expression of RANTES, MCP-1, interferon-inducible protein (IP-10) and Interferon-Inducible T-cell Alpha Chemoattractant (I-TAC), while IL-Iβ induces mainly IL-8 and epithelial neutrophil-activating peptide 78 (ENA-78).